Fluent material handling – with receiver or receiver coacting mea – Plural materials – material supplies or charges in a receiver – Plural charges from the same source
Reexamination Certificate
1999-09-08
2001-03-20
Recla, Henry J (Department: 3751)
Fluent material handling, with receiver or receiver coacting mea
Plural materials, material supplies or charges in a receiver
Plural charges from the same source
C435S286500, C436S180000
Reexamination Certificate
active
06202713
ABSTRACT:
The invention relates to a process and a device for series cultivation of organisms. An aspect of this invention relates to a process and a device for dosing liquids in which a liquid from a liquid supply tank is dosed into at least one container by means of a dosing device controlled by commands from a computer.
The biotechnological preparation of substances employs microorganisms which, through expression of their genetic material or implemented vectors, are capable of producing these substances. In order to attain a cost-effective production of the substances, conditions have to be created for the organisms under which they are able to achieve their maximum production capacity. These conditions depend on external factors such as toxic influences and the correct filling with substrate that is needed for the growth and production of the substances. Thus, for example, it has been found that only in certain concentrations does the addition of a substrate lead to good results for the biotechnological production of substances. If the substrate is underdosed, not enough nutrients are available to result in a high production of the desired product. However, overdosing of the substrate can mean that the substrate is no longer used exclusively for the production of the desired substance but also that additional, undesired by-products are formed which give rise to impurities that then have to be isolated with a great deal of effort. Diverting substrate into the production of other, undesired compounds is even associated with a diminished production of the desired product. These factors have to be determined experimentally. One way to determine these factors is series cultivation in shaking flasks under varying conditions.
For instance, German Utility Model No. G 94 19 230.8 discloses a device in which shaking flasks are filled with substrate from a dosing device. The dosing device conveys the substrate into a multiport plug valve from which supply lines branch off that lead into the shaking flasks. In this device, the shaking flasks are filled with substrate one after the other, whereby the multiport plug valve is switched over to the next position each time. The device of the utility model is used when series experiments are used to determine the substrate quantities that constitute the optimal conditions of exposure for the organisms during the production of biochemically prepared products. With this device, however, it is also possible to supply microorganisms with substrate for which the substrate itself is toxic if it exceeds a certain concentration. The device should meet extremely high standards in terms of its dosing accuracy so that no overdosing occurs. Therefore, the device of German Utility Model No. G 94 19 230.8 is operated by a computer program by means of which the user specifies the amount of substrate to be dosed into each shaking flask in the form of a dosing schedule. The dosing schedule can be different for each shaking flask so that each shaking flask can then be subjected to different experiment conditions.
The device of the utility model does achieve some good results, but it also entails drawbacks. For example, the number of shaking flasks that can be filled at the same time is limited to sixteen positions due to the design of the multiport plug valve. Due to the constant switching over of the multiport plug valve, its service life is limited to about two months. Over the course of time, inaccurate dosing can occur as a result of wear and tear of the material. The multiport plug valve cannot be thermally sterilized since it is mechanically fabricated and changes occur in the structure of the multiport plug valve in response to temperature fluctuations, leading to a misalignment of the contact surfaces and thus to leaks. As a consequence, the device according to the utility model can only be sterilized with chemical agents. In this case, however, sterilization agents or their degradation products can be adsorbed on the walls of the valve or of the lines and can later be entrained into the shaking flask as the latter is filled during a subsequent dosing procedure. As a result, the metabolism of the organisms can be impacted upon, which can lead to erroneous experiment results.
Since the shaking flasks can only be filled one at a time, this method calls for a program which can take into account deviations from the dosing of the theoretically underlying dosing schedule. In this case, however, the deviations are not prevented right from the start but rather are merely corrected after the fact. A—potentially serious—underdosing vis-à-vis the actual target dosage can occur.
Moreover, the substrates to be dosed are usually highly viscous media that have to be fed in via conveying means during the filling of the shaking flasks. This gives rise to back pressure which slows down the dosing—in other words, not the entire amount of substrate that needs to be dosed is actually conveyed into the shaking flasks. After the theoretical dosing time has elapsed, the multiport plug valve is switched over to the next position and the backed-up amount of substrate is entrained into the next shaking flask. If a series of shaking flasks are dosed one after the other in this manner, a substrate quantity accumulates by the time the last shaking flask to be filled is reached, and this amount is discharged into a relief vessel after the end of a filling cycle. This essentially corresponds to the amount of substrate that was entrained because of the build-up of the back pressure and that was thus erroneously not dosed into the shaking flasks.
Due to the dosing sequence prescribed according to the state of the art, when different dosing functions are employed for the different shaking flasks, temporary underdosing can occur, which can no longer be remedied. As a result, the dosage present in the individual flasks deviates more and more from the actually desired target value as the experiment progresses.
Moreover, this entails operating downtimes, when the substrate supply has to be refilled after a cycle of filling operations. This prolongs the experiment times and leads to interruptions in the dosing which, in turn, does not result in an optimal adaptation of the substrate addition to the actually desired experiment series.
Therefore, it is the objective of the invention to create a process and a device with which dosing can be carried out that precisely meets the requirements in terms of the needed volumes at every point in time during an experiment. Toxic effects stemming from the substrate should be further minimized. Downtimes during operation should be reduced to a minimum and substrate entrainment should be avoided.
The device should also be thermally sterilizable and its service life should be ensured over prolonged periods of time without interruption due to maintenance work.
Thus, this invention provides a computer-controlled process and a device for carrying out the process in which liquid for a liquid supply tank
8
is dosed into at least one container
1
by means of a dosing device
5
controlled by commands from a computer, wherein:
a dosing schedule for each container is selected and programmed into the computer;
each container is dosed in accordance with the dosing schedule;
after each dose, the volume of liquid delivered to a container
1
is measured by the computer and stored in the computer as computer data;
each subsequent dose of liquid to each container
1
is selected by the computer in accordance with the data regarding the amount already dosed as well as in accordance with the dosing schedule, so that at the point in time for a subsequent dose, the volume of the dose corresponds to the actual requirement but is as least as large a minimum dosing volume that is the least that can be dosed.
With the process and the device according to the invention, a freely selectable number of shaking flasks can be filled more precisely with substrate without a predefined sequence. The individual shaking flasks are filled without overdosing, and substantial underdosing is avoide
Altenbach-Rehm Juta
Drescher Thomas
Weuster-Botz Dirk
Connolly Bove & Lodge & Hutz LLP
deVore Peter
Forschungszentrum Julich GmbH
Recla Henry J
LandOfFree
Method and device for series cultivation of organisms does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method and device for series cultivation of organisms, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method and device for series cultivation of organisms will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2527989